This invention relates to a method and apparatus for detecting the concentration of chemical species in a solution such as the concentration of immunochemical species.
Accurate, more precise methods of detecting the presence and concentration of various chemical species in a solution, both in vivo and in vitro, have been the subject of much research and numerous development efforts. See, for example, U.S. Pat. Nos. 3,966,580, 3,574,062, 3,843,446, 3,999,122, 3,831,432 and 4,238,757.
As explained in the above-cited patents, detecting the presence and concentration of chemical species in a solution requires that the chemical sensor exhibit selectivity, i.e., the ability to detect a particular chemical species to the exclusion of others. Immunochemical reactions, by their nature, are highly selective in that certain immunochemical species, e.g., antibodies, react or bond to only certain other immunochemical species, e.g., antigen. Because of this selectivity characteristic, numerous attempts have been made to develop direct chemical sensors for sensing various immunochemical species. See, for example, Janata, J., Principles of Chemical Sensors, Plenum Publishing Co., New York, New York, 1989. These attempts, however, have generally been unsuccessful for the following reasons: (1) selective bonding between the antibody and corresponding antigen or hapten (low molecular weight antigen) is progressive in that the strength of the bond between the immunochemical species increases with time--as a result, this bond eventually becomes so strong that a permanent antibody/antigen complex is formed and so the interaction becomes irreversible and continued detection or sensing is prevented; and (2) a reliable transduction mode is not known for direct immunochemical reactions (transduction, in this context, means conversion or transformation of the chemical bonding event into a measurable physical signal).